Method for the conversion of nitriles to aldehydes



United States Patent METHOD FOR THE CONVERSION OF NITRILES T0 ALDEHYDES No Drawing. Application September 30, 1952,

Serial No. 312,416

2 Claims. (Cl. 260-609) The present invention concerns a convenient, general method for reducing aliphatic nitrilcs to the corresponding aldehydes, and more particularly, a process for the reduction of an ortho ester to an acetal.

Aldehydes are useful, among other things, in the manufacture of chemicals, dyes, intermediates, disinfectants, and in organic synthesis and medicine. Transformation of aliphatic nitriles to aldehydes was previously accomplished by three practical methods, namely, pyrolysis, the Stephen reduction and the Rosemund reduction. In the pyrolysis method, the nitrile is hydrolyzed to a carboxylic acid. Then a mixture of carboxylic acid and formic acid (or the calcium or barium salts) are pyrolyzed in the presence of a metallic oxide catalyst, the equations being:

A ROOOH HCOOH RCHO COrifl) The formation of calcium carbonate on pyrolyzing the mixture of salts (or of carbon dioxide in the case of the mixture of acids) can take place in the above two ways, giving rise to a mixture of a ketone and an aldehyde. However, the yields of aldehydes are very poor.

The Stephen reduction consists of treating a nitrile in dry ether with anhydrous stannous chloride and hydrogen chloride gas. An intermediate aldimine, stannic chloride complex, is formed, which can be hydrolyzed to the aldehyde, the equation being:

RON H01 RC=NH SnCh 1 H (RCH=NH.HGl):SnC1t -0 811014 NHtCl RCHO This method is not as general as is claimed. The yields are highly variable with ditferent nitriles and in some instances no yield at all is produced.

The Rosemund reduction involves the hydrogenation of an acid chloride with palladium-barium sulphate as a. catalyst. The acid chloride must first be prepared from a nitrile by hydrolysis to the acid, then treated with phosphorus pentachlo'n'de or thionyl chloride, the equation being:

H10 SOCli RCN RCOOH RCOCI Pd RCOCH-H: RCHO+HOl IBaSOe in order to accomplish this reduction, high pressure equip ment is required and the yield of aldehyde varies greatly. An object of the invention is to provide a process for the conversion of aliphatic nitriles to aldehydes wherein the above mentioned disadvantages are eliminated.

Another object of the invention is to provide a proc- 2,786,872 Patented Mar. 26, 1957 ess for the conversion of nitriles to aldehydes that yields a stable acetal of the aldehyde as the end product.

Other objects and many of the attendant advantages of this invention will be readily appreciated as the same becomes better understood by reference to the following detailed description.

The subject method for the conversion of aliphatic nitriles to aldehydes involves a hitherto unknown reaction of lithium aluminum hydride, the reduction of an ortho ester to an acetal. A nitrile is treated with alcohol in the presence of hydrogen chloride under anhydrous conditions to yield the imino ether hydrochloride. Such imino ether hydrochloride is then alcoholyzed to the corresponding ortho ester. Treatment of the ortho ester with lithium aluminum hydride yields the acetal, said acetal being readily hydrolyzed to the aldehyde in the presence of an acid, the equation being:

out EtOH 2EtOH RCEN R|C=NH.HG1 no om om on:

OEt LiAlH, H+ Ro-0Et nomono, nono A specific method of reducing aliphatic nitriles to the corresponding aldehydes was developed in the course of an investigation of a synthesis of methionine-u-C It was desired to prepare 18-methylmercaptopropionaldehyde in good yield from cyanide-labeled fl-rnethylmercaptopropionitrile.

Methyl and ethyl esters of ortho-B-methylmercaptopropionic acid were obtained from fi-methylmercaptopropionitrile, according to McElvains procedure described in the Journal of the American Chemical Society,

vol. 64, page 1824, 1942, by S. M. McElvain and J. N. Nelson. Methyl ester, 57.6% yield B. P. 51-52 (l mm.), (calculated for C'1H1eOsS: C, 46.59; H, 8.89. Found: C, 46.98; H, 8.68). Ethyl ester, 65.5% yield. B. P. 7172 (0.8 mm.), (calculated for CroHazOsS: C, 53.98; H, 9.90. Found: C, 54.35; H, 9.89). The following method was then used to reduce the ortho esters to the corresponding acetals:

One quarter of a molar equivalent of lithium aluminum hydride (l M other solution) was added to a boiling solution (0.33 M) of the ortho ester in benzene. The mixture was refluxed four hours. The complex was clecomposed with Rochelle salt solution (30%) and the benzene extract was dried and distilled.

Both methyl and ethyl acetals of fi-methylmeroapto propionaldehyde were obtained in good yield. Dimethyl acetal, 97% yield, B. P. 73 (0.9 mm.), (calculated for CeHnOzS: C, 46.98; H, 9.33. Found: C, 47.11; H, 8.95). Diethyl acetal, 73% yield, B. P. 68-74 (0.7 mm.), (calculated for CsHraOzS: C, 53.84; H, 10.12. Found: C, 54.13; H, 9.81). The acetals produced by this process are readily hydrolyzed to B-methylmercaptopropion-aldehyde. The 2,4 dinitrophenylhydrazone (M. P. 1195-1205") was prepared from each acetal. Mixed melting points with an authentic sample showed no depression.

Apparently this reduction is of general applicability since the orthoformic, orthoacetic, and orthovaleric ethyl esters, prepared from the nitriles, were converted to the corresponding acetals in good yields.

Aliphatic aldehydes prepared by the aforementioned procedure are obtained as stable acetals, which are not subject to deterioration because of condensation and polymerization. These acetals can be purified conveniently and safely by distillation without loss of material, before converting them to the more sensitive aldehydes.

t W W 2 ,786,872

Qnly standard organic lghoretory equipment without high te erature or high pressure techniques is required td'iiri inventioli. The pyrsi 'stsfsrepssirream;- tion and Rosemund reductions yield directly the aliphatic aldehydes, which are more difiicult to handle because of their extreme retictivity. Y v

It is contemplated that ortho esters prepared :from alcohols other Tth an methyl and ethyl {alcohol can be substituted in the vabove procedure, the equation being where R is an alkyl radical and R is either an alkyl or aryl group. Mixed ortho esters can be used in which R groups'ditfer from one another. Also under proper conditions, other metal hydride-s (such as lithium borohydride or sodium borohydride) will reduce ortho esters to acetals.

From the foregoing it is seen that n metal hydride can reduce an ortho ester to anacetel, said process of converting a nitrile to an aldehyde yielding a stable acetal of the aldehyde as an end product.

Obviously many modifications end variations of the present invention ere possible in the light of the above teachings. It is therefore to be understood that within thescope of'theappended claims the invention can be PEE EFQ .sthsrme has as seesiliselly tis iibti- What is claimed is:

1. The process for the preparation of the ethyl acetal of fl-methylmercaptopropionaldehyde from the corresponding ortho ester comprising the steps of adding lithium aluminum hydride to a boiling solution of such ortho .ester'in benzene, reflugiingsziid rriixtu're, and decomposing the complex.

The process tor t he preparntion of the .ethyl ecetal of ,dl-methylmerceptopropionnldehyde comprising the steps .of edging pne uarter of a molar equivalent of lithium aluminum hydride (1 M ether solution) to boilingsolution (Q33 M) of an ortho ester of ortho-t. methylrnercaptopropiQflic lcid in benzene, refluxing four hours, decomposing with" Rochelle salt solution drying and distilling the benzene extract.

Kritchevsky: I. Am. Chem. Soc, p. 487, March 1943. WendlenSlateset 111.: John Am. Chem. Soc, vol. 73, pp. 719-724, 195.1. 

1. THE PROCESS FOR THE PREPARATION OF THE ETHYL ACETAL OF B-METHYLMERCAPTOPROPIONALDEHYDE FROM THE CORRESPONDING ORTHO ESTER COMPRISING THE STEPS OF ADDING LITHIUM ALUMINUM HYDRIDE TO A BOILING SOLUTION OF SUCH ORTHO ESTER IN BENZENE, REFLUXING SAID MIXTURE, AND DECOMPOSING THE COMPLEX. 